Orange rind could aid search for anti-cancer, anti-obesity drug

July 26, 2013
| by Nicole White

Not only is a single protein now believed to be implicated in three of the most serious health threats today – cancer, diabetes and obesity – scientists are currently charting the course toward clinical trials targeting the protein.

Researchers are interested in compounds derived from orange rinds that have the potential to inhibit a protein known as RLIP76, which has been linked to cancer and obesity.

City of Hope researchers recently published a study linking the protein, known as RLIP76, and the gene that produces it directly to obesity, garnering much attention for their work.

“Can we cure obesity without modifying our diet or exercising more?” Airtalk’s Larry Mantle asked in a story on KPCC.

One gene now appears linked to obesity, metabolic syndrome and diabetes, said Sanjay Awasthi, M.D., professor in the Division of Molecular Diabetes Research at City of Hope. He led the study with Sharad Singhal, Ph.D., professor in the Department of Diabetes and Metabolic Diseases Research. When you get rid of this gene in a mouse, it would appear that the mouse can’t get obese, it can’t get diabetes, it can’t get high cholesterol and it can’t get cancer, Awasthi said.

The findings are the most recent in a string of dozens of peer-reviewed papers on RLIP that Awasthi and Singhal have published together. The next challenge will be to confirm their findings with trials in human patients – and of course findings in mice often do not correlate to results in human trials.

So far, Awasthi and Singhal have linked RLIP76 to 10 different cancers, as well as to obesity. The protein’s function is to pump toxins out of cells. Regular cells have small amounts of the protein, but cancer cells produce excess amounts of the protein – so much that the protein pushes out medicines attempting to fight the cancer.

The researchers are currently seeking funding for cancer clinical trials and say that a clinical trial focused on obesity could occur within six to eight months of obtaining funds. Grants from several sources are currently pending. One of the compounds the team hopes to investigate is an orange rind extract that belongs to a family of molecules called flavinols, and has the potential to inhibit the protein.

“The orange peel extract is, by definition, an antioxidant, and it has potential to fight these diseases through a number of mechanisms,” Awasthi said.

First, the extract could reduce oxidative stress – which is known to exacerbate obesity and has been linked to other diseases. As a person breathes, the body constantly reacts to the oxygen, and these reactions can produce potentially destructive molecules called free radicals, which can cause damage to proteins, membranes and genes. This damage is called oxidative stress. The extract also has the potential to inhibit the chemical pathways used by RLIP76 and to genetically reduce expression of the protein.

The extract could be formulated in a variety of ways to be tested against different cancers. The drug being considered for production for an obesity trial would be an oral medication.

City of Hope’s ability to manufacture the drugs needed for clinical trials contributes to how quickly a trial can happen once funding is in place, Awasthi said.

“I’m fortunate to be at City of Hope where we have developed techniques and facilities for good manufacturing practice,” he said.

While Awasthi and Singhal hope that their laboratory research will translate into meaningful treatments – they do not recommend anyone start chowing down on orange rind in hopes of narrowing their waistlines.

“The only thing that will inoculate people against gaining weight is caloric restriction and exercise, that’s what we know at this time,” Awasthi said. “Reducing stress is also a good strategy.”